tbuckley/cabot-search huggingface dataset:
Advances in the polymeric delivery of nucleic acid vaccines
Authors: Gang Chen, Bowen Zhao, Elena F. Ruiz, Fuwu Zhang
Journal: Theranostics (2022)

Nucleic acid vaccines, especially messenger RNA (mRNA) vaccines, display unique benefits in the current COVID-19 pandemic.The application of polymeric materials as delivery carriers has greatly promoted nucleic acid vaccine as a promising prophylactic and therapeutic strategy.The inherent properties of polymeric materials render nucleic acid vaccines with excellent in vivo stability, enhanced biosafety, specific cellular uptake, endolysosomal escape, and promoted antigen expression.Although polymeric delivery of nucleic acid vaccines has progressed significantly in the past decades, clinical translation of polymer-gene vaccine systems still faces insurmountable challenges.This review summarizes the diverse polymers and their characterizations and representative formulations for nucleic acid vaccine delivery.We also discussed existing problems, coping strategies, and prospect relevant to applications of nucleic acid vaccines and polymeric carriers.This review highlights the rational design and development of polymeric vaccine delivery systems towards meeting the goals of defending serious or emerging diseases.
<i>Eucommiae cortex</i> polysaccharides mitigate obesogenic diet-induced cognitive and social dysfunction via modulation of gut microbiota and tryptophan metabolism
Authors: Penghao Sun, Mengli Wang, Zhuoni Li, Jingjing Wei, Feng Liu, Wei Zheng, Xiaoyan Zhu, Xuejun Chai, Shanting Zhao
Journal: Theranostics (2022)

The high fat and sucrose diet, known as the obesogenic diet (OD), has been related to low-grade chronic inflammation and neurodevelopmental disorders. Emerging evidence suggests that OD influences cognitive and social function via the gut-brain axis. However, the effects of OD during adolescence on future health have been unclear. Meanwhile, the underlying mechanisms and effective interventions are not fully understood. Polysaccharides, one of the most abundant substances in the
Single-cell landscape reveals active cell subtypes and their interaction in the tumor microenvironment of gastric cancer
Authors: Yumin Li, Xueda Hu, Ruichai Lin, Guangyu Zhou, Lulu Zhao, Dongbing Zhao, Yawei Zhang, Wenbin Li, Yueming Zhang, Peiqin Ma, Hu Ren, Xinhui Liao, Penghui Niu, Tongbo Wang, Xiaojie Zhang, Wanqing Wang, Ranran Gao, Qibin Li, George Church, Jie He, Yingtai Chen
Journal: Theranostics (2022)

Background: Gastric cancer remains the third most common cause of cancer-related death worldwide.The development of novel therapeutic strategies for gastric cancer requires a deep understanding of the tumor cells and microenvironment of gastric cancer.Methods: We performed the single-cell RNA sequencing (scRNA-seq) on nine untreated non-metastatic gastric cancer patients.The transcriptomic atlas and ligand-receptor-based intercellular communication networks of the single cells were characterized.Results: Here, we profiled the transcriptomes of 47,304 cells from nine patients with gastric cancer.Tregs cells were significantly enriched in the gastric tumor tissues with increased expression of immune suppression related genes, which suggest a more immunosuppressive microenvironment.We also observed the absence of separate exhausted CD8+ T cell cluster, and the low expression level of exhaustion markers PDCD1, CTLA4, HAVCR2, LAG-3, and TIGIT in those specific cells.These may serve as molecular-level evidence for the limited benefit of immunotherapy among gastric cancer patients.In addition, we found ACKR1 specifically expressed in tumor endothelial cells, associated with poor prognosis in the cohort data and potentially provided a novel target of gastric cancer treatment.Furthermore, the tight interaction between endothelial cells and fibroblast implied the important roles of fibroblast in tumor angiogenesis and the maintenance of tumor vasculature. Conclusions:In conclusion, this single-cell atlas provide understanding the cellular heterogeneity from molecular level in gastric cancer and will serve as a valuable resource for developing innovative early and companion diagnostics, as well as discovering novel targeted therapies for gastric cancer.
Calixarene-modified albumin for stoichiometric delivery of multiple drugs in combination-chemotherapy
Authors: Ying Wang, Zhanzhan Zhang, Xinzhi Zhao, Lina Xu, Yadan Zheng, Hua-Bin Li, Dong-Sheng Guo, Linqi Shi, Yang Liu
Journal: Theranostics (2022)

Rationale: In combination chemotherapy, the molar ratio of drugs is a critical parameter that determines the synergistic effects. However, most co-delivery vectors are incapable of maintaining the optimal molar ratio of drugs throughout the delivery process. Herein, a calixarene-modified albumin (CaMA), which can co-deliver multiple drugs with precise control of the drug ratio, is presented. Methods: CaMA was prepared by chemically conjugating multiple sulfonate azocalix[4]arenes (SAC4A) onto the surface of bovine serum albumin (BSA). The precise drug loading and synchronous drug release were measured using fluorescence spectroscopy. Mouse tumor cell 4T1 and 4T1-bearing mice were used to evaluate the combined effects of mitomycin C (MMC) and doxorubicin (DOX) in vitro and in vivo. Results: With multiple hypoxia-responsive calixarenes conjugated onto a single albumin molecule, CaMA achieved precise drug loading and synchronous release of multiple drugs into the tumor microenvironment. This unique drug loading and release mechanism ensures that CaMA maintains the drug ratio from the initial drug loading to the release site, providing a solid foundation for multi-drug combination therapy with the goal of achieving predictable therapeutic outcomes in vivo. The delivery of the model drug combination MMC and DOX at a prescreened ratio via CaMA achieved significantly enhanced tumor suppression and reduced systemic toxicity. Conclusions: This stoichiometric delivery feature makes CaMA a powerful tool for the development of combination chemotherapy and personalized medications for cancer treatment.
Optic chiasmatic potential by endoscopically implanted skull base microinvasive biosensor: a brain-machine interface approach for anterior visual pathway assessment
Authors: Yikui Zhang, Shengjian Lu, Shenghai Huang, Zhonghao Yu, Tian Xia, Mengyun Li, Chen Yang, Yiyang Mao, Boyue Xu, Lixu Wang, Lei Xu, Jieliang Shi, Xingfang Zhu, Senmiao Zhu, Si Zhang, Haohua Qian, Yang Hu, Wei Li, Yunhai Tu, Wencan Wu
Journal: Theranostics (2022)

Background: Visually evoked potential (VEP) is widely used to detect optic neuropathy in basic research and clinical practice.Traditionally, VEP is recorded non-invasively from the surface of the skull over the visual cortex.However, its trace amplitude is highly variable, largely due to intracranial modulation and artifacts.Therefore, a safe test with a strong and stable signal is highly desirable to assess optic nerve function, particularly in neurosurgical settings and animal experiments.Methods: Minimally invasive trans-sphenoidal endoscopic recording of optic chiasmatic potential (OCP) was carried out with a titanium screw implanted onto the sphenoid bone beneath the optic chiasm in the goat, whose sphenoidal anatomy is more human-like than non-human primates.Results: The implantation procedure was swift (within 30 min) and did not cause any detectable abnormality in fetching/moving behaviors, skull CT scans and ophthalmic tests after surgery.Compared with traditional VEP, the amplitude of OCP was 5-10 times stronger, more sensitive to weak light stimulus and its subtle changes, and was more repeatable, even under extremely low general anesthesia.Moreover, the OCP signal relied on ipsilateral light stimulation, and was abolished immediately after complete optic nerve (ON) transection.Through proof-of-concept experiments, we demonstrated several potential applications of the OCP device: (1) real-time detector of ON function, (2) detector of region-biased retinal sensitivity, and (3) therapeutic electrical stimulator for the optic nerve with low and thus safe excitation threshold.Conclusions: OCP developed in this study will be valuable for both vision research and clinical practice.This study also provides a safe endoscopic approach to implant skull base brain-machine interface, and a feasible in vivo testbed (goat) for evaluating safety and efficacy of skull base brain-machine interface.
Influences of age, race, and sex on extracellular vesicle characteristics
Authors: Nicole Noren Hooten, Anjali M. Byappanahalli, Mya Vannoy, Victor Omoniyi, Michele K. Evans
Journal: Theranostics (2022)

Recent attention has focused on the use of extracellular vesicles (EVs) as biological indicators of health and disease.These small, nano-sized membrane bound vesicles are secreted from cells into the extracellular space and can be readily isolated from bodily fluids.EVs can carry various bioactive molecules as cargo including DNA, RNA, proteins, and lipids.These EVs can provide a snapshot of the cell of origin and a window of opportunity to assess normal physiological states as well as pathophysiological states.For EVs to further develop as potential biomarkers of disease, it is important to characterize whether these vesicles and their associated cargo are altered in the context of demographic factors.Here, we summarize the current literature on how demographics such as age, race, and sex affect the levels and cargo of EVs.Age and sex influence both EV cargo and concentration while race studies report differences mostly in EV protein cargo.This review also identifies areas of future research and important considerations for the clinical use of EVs as biomarkers.
Development of human cartilage circadian rhythm in a stem cell-chondrogenesis model
Authors: Mark A Naven, Leo A.H. Zeef, Shiyang Li, Paul A Humphreys, Christopher A Smith, Dharshika Pathiranage, Stuart Cain, Steven Woods, Nicola Bates, Manting Au, Chunyi Wen, Susan J Kimber, Qing-Jun Meng
Journal: Theranostics (2022)

The circadian clock in murine articular cartilage is a critical temporal regulatory mechanism for tissue homeostasis and osteoarthritis. However, translation of these findings into humans has been hampered by the difficulty in obtaining circadian time series human cartilage tissues. As such, a suitable model is needed to understand the initiation and regulation of circadian rhythms in human cartilage.
Activatable NIR-II organic fluorescent probes for bioimaging
Authors: Xiaoning Zhang, Shasha Li, Huizhen Ma, Hao Wang, Ruiping Zhang, Xiao-Dong Zhang
Journal: Theranostics (2022)

NIR-II imaging is developed rapidly for noninvasive deep tissue inspection with high spatio-temporal resolution, taking advantage of diminished autofluorescence and light attenuation.Activatable NIR-II fluorescence probes are widely developed to report pathological changes with accurate targeting, among which organic fluorescent probes achieve significant progress.Furthermore, the activatable NIR-II fluorescent probes exhibited appealing characteristics like tunable physicochemical and optical properties, easy processability, and excellent biocompatibility.In the present review, we highlight the advances of activatable NIR-II fluorescence probes in design, synthesis and applications for imaging pathological changes like reactive oxygen species (ROS), reactive nitrogen species (RNS), reactive sulfur species (RSS), pH, hypoxia, viscosity as well as abnormally expressed enzymes.This non-invasive optical imaging modality shows a promising prospect in targeting the pathological site and is envisioned for potential clinical translation.
Specific (sialyl-)Lewis core 2 <i>O</i>-glycans differentiate colorectal cancer from healthy colon epithelium
Authors: Katarina Madunić, Oleg A Mayboroda, Tao Zhang, Julia Weber, Geert-Jan Boons, Hans Morreau, Ronald van Vlierberghe, Tom van Wezel, Guinevere S M Lageveen-Kammeijer, Manfred Wuhrer
Journal: Theranostics (2022)

Cells are covered with a dense layer of carbohydrates, some of which are solely present on neoplastic cells. The so-called tumor-associated carbohydrate antigens (TACAs) are increasingly recognized as promising targets for immunotherapy. These carbohydrates differ from those of the surrounding non-cancerous tissues and contribute to the malignant phenotype of the cancer cells by promoting proliferation, metastasis, and immunosuppression. However, due to tumor tissue heterogeneity and technological limitations, TACAs are insufficiently explored. Methods: A workflow was established to decode the colorectal cancer (CRC)-associated O-linked glycans from approximately 20,000 cell extracts. Extracts were obtained through laser capture microdissection of formalin fixed paraffin embedded tissues of both primary tumors and metastatic sites, and compared to healthy colon mucosa from the same patients. The released O-glycans were analyzed by porous graphitized carbon liquid chromatography-tandem mass spectrometry in negative ion mode. Results: Distinctive O-glycosylation features were found in cancerous, stromal and normal colon mucosal regions. Over 100 O-linked glycans were detected in cancerous regions with absence in normal mucosa. From those, six core 2 O-glycans were exclusively found in more than 33% of the cancers, carrying the terminal (sialyl-)LewisX/A antigen. Moreover, two O-glycans were present in 72% of the analyzed cancers and 94% of the investigated cancers expressed at least one of these two O-glycans. In contrast, normal colon mucosa predominantly expressed core 3 O-glycans, carrying α2-6-linked sialylation, (sulfo-)LewisX/A and Sda antigens. Conclusion: In this study, we present a novel panel of highly specific TACAs, based upon differences in the glycomic profiles between CRC and healthy colon mucosa. These TACAs are promising new targets for development of innovative cancer immune target therapies and lay the foundation for the targeted treatment of CRC.
3D-bioprinting ready-to-implant anisotropic menisci recapitulate healthy meniscus phenotype and prevent secondary joint degeneration: Erratum
Authors: Ye Sun, Yuxin Zhang, Qiang Wu, Feng Gao, Yongzhong Wei, Yimin Ma, Wenbo Jiang, Kerong Dai
Journal: Theranostics (2022)

[This corrects the article DOI: 10.7150/thno.54864.].
Recapitulating influenza virus infection and facilitating antiviral and neuroprotective screening in tractable brain organoids
Authors: Xiaodong Zhang, Haishuang Lin, Liangzhen Dong, Qing Xia
Journal: Theranostics (2022)

Human pluripotent stem cell derived brain organoids offer an unprecedented opportunity for various applications as in vitro model.Currently, human brain organoids as models have been used to understand virus-induced neurotoxicity.Methods: The brain organoids were separately challenged by multiple viruses including influenza viruses (H1N1-WSN and H3N2-HKT68), Enteroviruses (EV68 and EV71) and Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) to investigate the impaired effect of these viruses on human brain development. Results:The brain organoids challenged by influenza viruses had decreased overall organoid size, while enteroviruses infected brain organoids displayed the opposite result.Then, we found WSN preferentially infected MAP2+ neurons compared to SOX2+ neural stem cells (NSCs) and GFAP+ astrocytes in brain organoids, and induced apoptosis of NSCs and neurons, and released inflammatory factors (TNF-α, INF-γ, and IL-6), facilitating brain damage.Furthermore, transcriptional profiling revealed several co-upregulated genes (CSAG3 and OAS2) and co-downregulated genes (CDC20B, KCNJ13, OTX2-AS1) after WSN infection for 24 hpi and 96 hpi, implicating target for antiviral drugs development.Finally, we explored compound PYC-12 could significantly suppress virus infection, apoptosis, and inflammatory responses.Conclusions: Collectively, we established a tractable experimental model to investigate the impact and mechanism of virus infection on human brain development.
Docetaxel remodels prostate cancer immune microenvironment and enhances checkpoint inhibitor-based immunotherapy
Authors: Zehua Ma, Weiwei Zhang, Baijun Dong, Zhixiang Xin, Yiyi Ji, Ruopeng Su, Kai Shen, Jiahua Pan, Qi Wang, Wei Xue
Journal: Theranostics (2022)

Background: Prostate cancer is usually considered as immune "cold" tumor with poor immunogenic response and low density of tumor-infiltrating immune cells, highlighting the need to explore clinically actionable strategies to sensitize prostate cancer to immunotherapy.In this study, we investigated whether docetaxel-based chemohormonal therapy induces immunologic changes and potentiates checkpoint blockade immunotherapy in prostate cancer.Methods: We performed transcriptome and histopathology analysis to characterize the changes of prostate cancer immune microenvironment before and after docetaxel-based chemohormonal therapy.Furthermore, we investigated the therapeutic benefits and underlying mechanisms of chemohormonal therapy combined with anti-PD1 blockade using cellular experiments and xenograft prostate cancer models.Finally, we performed a retrospective cohort analysis to evaluate the antitumor efficacy of anti-PD1 blockade alone or in combination with docetaxel-based chemotherapy.Results: Histopathology assessments on patient samples confirmed the enrichment of tumor-infiltrating T cells after chemohormonal therapy.Moreover, we found that docetaxel activated the cGAS/STING pathway in prostate cancer, subsequently induced IFN signaling, resulting in lymphocytes infiltration.In a xenograft mouse model, docetaxel-based chemohormonal therapy prompted the intratumoral infiltration of T cells and upregulated the abundance of PD1 and PD-L1, thereby sensitizing mouse tumors to the anti-PD1 blockade.To determine the clinical significance of these results, we retrospectively analyzed a cohort of 30 metastatic castration-resistant prostate cancer patients and found that docetaxel combined with anti-PD1 blockade resulted in better prostate-specific antigen progression-free survival when compared with anti-PD1 blockade alone.Conclusions: Our study demonstrates that docetaxel activates the antitumoral immune response and facilitates T cell infiltration in a cGAS/STING-dependent manner, providing a combination immunotherapy strategy that would improve the clinical benefits of immunotherapy.
MiR-155 deficiency protects renal tubular epithelial cells from telomeric and genomic DNA damage in cisplatin-induced acute kidney injury
Authors: Qing Yin, Ya-Jie Zhao, Wei-Jie Ni, Tao-Tao Tang, Yao Wang, Jing-Yuan Cao, Di Yin, Yi Wen, Zuo-Lin Li, Yi-Lin Zhang, Wei Jiang, Yue Zhang, Xiao-Yu Lu, Ai-Qing Zhang, Wei-Hua Gan, Lin-Li Lv, Bi-Cheng Liu, Bin Wang
Journal: Theranostics (2022)

: Cisplatin nephrotoxicity is an important cause of acute kidney injury (AKI), limiting cisplatin application in cancer therapy. Growing evidence has suggested that genome instability, telomeric dysfunction, and DNA damage were involved in the tubular epithelial cells (TECs) damage in cisplatin-induced AKI (cAKI). However, the exact mechanism is largely unknown.
Requirement of hippocampal DG nNOS-CAPON dissociation for the anxiolytic and antidepressant effects of fluoxetine
Authors: Hu-Jiang Shi, Dan-Lian Wu, Rong Chen, Na Li, Li-Juan Zhu
Journal: Theranostics (2022)

Background: Adult hippocampal neurogenesis and synaptic plasticity are necessary for the behavioral response to the selective serotonin reuptake inhibitor (SSRI) fluoxetine, but the molecular mechanisms underlying these effects are only partially understood.Methods: Anxiety and depressive-like behaviors in mice were developed by chronic mild stress (CMS) or chronic corticosterone (CORT) treatment.Pharmacological and genetic approaches were used to investigate the role of the neuronal nitric oxide synthase (nNOS)-carboxy-terminal PDZ ligand of nNOS (CAPON) interaction in behavioral and neuroplasticity effects of serotoninergic system.Molecular biological and morphological studies were performed to examine the mechanisms underlying the behavioral effects of nNOS-CAPON interaction that modulated by 5-HT1A receptor (5-HT1AR).Results: Fluoxetine prevented chronic stress-induced nNOS-CAPON upregulation and coupling in the dentate gyrus (DG), and promoting nNOS-CAPON association weakened the anxiolytic and antidepressant effects of fluoxetine in stressed mice.The chronic fluoxetine elevated 5-HT and 5HT1AR agonist 8-OH-DPAT decreased the expression and binding of nNOS with CAPON, whereas 5-HT1AR antagonist NAN-190 had the opposite effects.Importantly, augmenting nNOS-CAPON binding neutralized 8-OH-DPAT-upregulated spine density of DG granule cells and well-characterized synaptic-related proteins, including brain-derived neurotrophic factor (BDNF) and phosphorylation of extracellular signal regulated kinase (ERK), cAMP-response element binding protein (CREB), and synapsin in the DG and abolished the anxiolytic and antidepressant-like effects of 8-OH-DPAT.In contrast, dissociation of nNOS from CAPON rescued the effects of NAN-190 on behavior and neuroplasticity.Conclusion: Taken together, our results indicated that fluoxetine modifies mood behaviors and hippocampal neuroplasticity by disrupting the nNOS-CAPON interaction that links postsynaptic 5-HT1AR activation.
Integrated multi-omics characterization of KRAS mutant colorectal cancer
Authors: Wei Chong, Xingyu Zhu, Huicheng Ren, Chunshui Ye, Kang Xu, Zhe Wang, Shengtao Jia, Liang Shang, Leping Li, Hao Chen
Journal: Theranostics (2022)

KRAS mutation is the most frequent oncogenic aberration in colorectal cancer (CRC).The molecular mechanism and clinical implications of KRAS mutation in CRC remain unclear and show high heterogeneity within these tumors.Methods: We harnessed the multi-omics data (genomic, transcriptomic, proteomic, and phosphoproteomic etc.) of KRAS-mutant CRC tumors and performed unsupervised clustering to identify proteomics-based subgroups and molecular characterization.Results: In-depth analysis of the tumor microenvironment by single-cell transcriptomic revealed the cellular landscape of KRAS-mutant CRC tumors and identified the specific cell subsets with KRAS mutation.Integrated multi-omics analyses separated the KRAS-mutant tumors into two distinct molecular subtypes, termed KRAS-M1 (KM1) and KRAS-M2 (KM2).The two subtypes had a similar distribution of mutated residues in KRAS (G12D/V/C etc.) but were characterized by distinct features in terms of prognosis, genetic alterations, microenvironment dysregulation, biological phenotype, and potential therapeutic approaches.Proteogenomic analyses revealed that the EMT, TGF-β and angiogenesis pathways were enriched in the KM2 subtype and that the KM2 subtype was associated with the mesenchymal phenotype-related CMS4 subtype, which indicated stromal invasion and worse prognosis.The KM1 subtype was characterized predominantly by activation of the cell cycle, E2F and RNA transcription and was associated with the chromosomal instability (CIN)-related ProS-E proteomic subtype, which suggested cyclin-dependent features and better survival outcomes.Moreover, drug sensitivity analyses based on three compound databases revealed subgroup-specific agents for KM1 and KM2 tumors.Conclusions: This study clarifies the molecular heterogeneity of KRAS-mutant CRC and reveals new biological subtypes and therapeutic possibilities for these tumors.